Study of HLA-Haploidentical Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: ATG, fludarabine, cyclophosphamide, Total body irradiation.
- Who it may be relevant to
- Registry conditions: Sickle Cell Disease. Basic parameters: 16 years — 60 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
A Phase II Study of HLA-Haploidentical Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease
Overview
The study is a Phase II clinical trial. Patients will receive intensity modulated total body irradiation (TBI) at a dose of 3 Gy with standard fludarabine/ i.v. cyclophosphamide conditioning prior to human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplant (HSCT). The primary objective of the study is to determine the engraftment at Day +60 following HLA-haploidentical hematopoietic stem cell transplant protocol using immunosuppressive agents and low-dose total body irradiation (TBI) for conditioning and post-transplant cyclophosphamide in patients with sickle cell disease.
Interventions
- Drug ATG
0.5 mg/kg IV on day -9, and 2 mg/kg on days -8 and day -7 - Drug fludarabine
30 mg/m2 IVPB daily for day -6 (6 days before stem cell infusion) through day -2 - Drug cyclophosphamide
14.5 mg/kg IV on days -6 and -5 and 50 mg/kg/d on days +3 and +4 - Radiation Total body irradiation
3 Gy on day -1 - Procedure Stem cell infusion
Stem cell product infused according to BMT unit policy on day 0. - Drug Sirolimus
loading dose of 15 mg followed by 5 mg per day on day +5 - Drug mycophenolate mofetil
1 g every 8 h (until day 35) will be started on day 5
Primary outcome measures
- Estimate the number of patients who engraft by Day +60 [Time frame: Up to Day +60]
Secondary outcome measures (3)
- Disease free survival [Time frame: Up to Day +60]
- Overall survival [Time frame: Up to Day +60]
- Adverse Effects [Time frame: Up to Day +60]
Eligibility criteria
Patient Eligibility:
- Patients with sickle cell disease are eligible if they have any of the following complications:
1.1 Stroke or central nervous system event lasting longer than 24 hours 1.2 Frequent vaso-occlusive pain episodes, defined as ≥ 3 per year requiring emergency room, acute care center, hospital admissions, or home bedrest leading to absence from work or school. 1.3 Recurrent episodes of priapism, defined as ≥ 2 per year requiring emergency room visits 1.4 Acute chest syndrome with recurrent hospitalizations, defined as ≥ 2 lifetime events 1.5 Red-cell alloimmunization (≥ 2 antibodies) during long-term transfusion therapy 1.6 Bilateral proliferative retinopathy with major visual impairment in at least one eye 1.7 Osteonecrosis of 2 or more joints 1.8 Sickle cell nephropathy, defined by a GFR < 90mL/min/1.73m2 or the presence of macroalbuminuria (urine albumin > 300 mg/g creatinine) 1.9 Pulmonary hypertension, defined by a mean pulmonary arterypressure >25mmHg
- Age 16-60 years
- Karnofsky performance status of 60 or higher (Appendix A)
- Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40%
- Adequate pulmonary function, defined as diffusion lung capacity of carbon monoxide ≥ 50% predicted (after adjustment for hemoglobin concentration)
- Estimated GFR ≥ 50mL/min/1.73m2 as calculated by the modified MDRD equation
- ALT ≤ 3x upper limit of normal
- HIV-negative
- Patient is not pregnant
- Patient is able and willing to sign informed consent
- Patient does not have a fully HLA-matched sibling donor
- Patient has an HLA-haploidentical relative
Donor Eligibility Relatives (parents, offspring, siblings, aunts/uncles, cousins) will be tested by molecular typing of HLA class I (A, B, and C) and class II (DRB1) at low resolution. Only those that are an HLA-haploidentical match (≥ 4/8) will be considered as a potential donor. NOTE: If during testing, a fully HLA-matched sibling donor is found and is willing to donate his/her stem cells, the potential subject will not be eligible for this protocol.
Donor consent will be obtained as per standard protocol of the bone marrow transplant unit.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 1 center
- University of Illinois at Chicago — Chicago
Identifiers
NCT: NCT03121001 · 2016-1152